| Drug interactions
Monitor phenytoin concentrations closely if given concurrently with the following medications: Erythromycin, trimethoprim/sulfamethoxazole, amphotericin, fluconazole, miconazole, amiodarone, omeprazole and ranitidine which may increase phenytoin concentrations. Fluoroquinolones (e.g. ciprofloxacin, moxifloxacin), rifampicin, folic acid and calcium may decrease phenytoin concentrations. In the case of calcium, administration should be separated by at least 1 hour to reduce the interaction. Concurrent administration of phenytoin with phenobarbital (phenobarbitone) has variable effects on serum concentrations of either drug. Serum concentrations should be monitored for both drugs. Some medications are affected by phenytoin (monitor the concentration of the medication if possible): folic acid, thyroxine, vitamin D, calcium, corticosteroids (e.g. dexamethasone), caffeine, frusemide, digoxin and vecuronium may have their concentrations reduced. Phenytoin may also lower the blood concentrations of methadone, possibly manifesting withdrawal earlier in neonatal abstinence syndrome. Other interactions: Diazoxide may reduce the serum concentration of phenytoin and phenytoin may increase the hyperglycaemic effects of diazoxide. Dopamine used concurrently with phenytoin may cause profound hypotension. Beta-blockers (e.g. propranolol, sotalol) used concurrently with phenytoin may cause hypotension and may produce additive cardiac depressant effects.
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